Investigation of the sources of variability in the extracellular potential around neurons

The extracellular potential (EP) generated within the neuropil represents a summation of electrical activity arising from both neuron cell bodies and neurites throughout a volume of tissue. A complete understanding of the neuronal sources of variability in the EP is necessary to best apply spike sorting techniques and attain the most accurate representations of underlying neural spiking activity. This thesis presents the results from computer simulations of both single neuron and neuronal ensemble models regarding the contributions to spatial and temporal variability in the EP arising from the dendritic morphology, background synaptic activity, the spatial distribution of transmembrane currents, and synchronous neuronal firing. Cable models, single neuron dendritic models, and ensemble/tissue models are used quantify the impacts of morphological and electrophysiological discontinuities on spatial variability in the EP for the sample case of T-type calcium channel distributions in thalamic reticular nucleus (TRN) neurons. The results show that sharp discontinuities in the channel densities of transmembrane currents can lead to dipole-like arrangements of current sinks and sources aligned along the dendritic axis. Ensemble modeling of background synaptic noise under in vivo- and in vitro-like conditions of spontaneous, tonic firing suggests that the direct effect of postsynaptic currents (PSCs) on the EP is small compared to the indirect effects via modulation of intrinsic properties and the activation levels of other currents that shape the EP. Results from these ensemble models also suggest that low-frequency variations in the EP are more likely a result of the summation of synaptic or slow intrinsic currents as opposed to a superposition of fast spiking currents. Certain regions of the brain have been shown to possess intrinsic mechanisms for generating patterns of synchronous firing behavior within nearby neurons, such as gap junctions or field effect interactions. Results are presented for the spike sorting of simulated EPs containing highly synchronized spiking behavior which illustrate that interspike synchrony on the same order as the extracellular spike width can significantly degrade the performance of spike sorting routines. Finally, this computational investigation of EP variability highlights the level of modeling detail necessary to create biophysically-accurate representations of the EP.